A cluster randomised controlled trial of a web based decision aid to support parents' decisions about their child's Measles Mumps and Rubella (MMR) vaccination.

OBJECTIVE: To evaluate the effectiveness of a web based decision aid versus a leaflet versus, usual practice in reducing parents' decisional conflict for the first dose MMR vaccination decision. The, impact on MMR vaccine uptake was also explored. DESIGN: Three-arm cluster randomised controlled trial. SETTING: Fifty GP practices in the north of, England. PARTICIPANTS: 220 first time parents making a first dose MMR decision. INTERVENTIONS: Web, based MMR decision aid plus usual practice, MMR leaflet plus usual practice versus usual practice only, (control). MAIN OUTCOME MEASURES: Decisional conflict was the primary outcome and used as the, measure of parents' levels of informed decision-making. MMR uptake was a secondary outcome. RESULTS: Decisional conflict decreased post-intervention for both intervention arms to a level where, parents could make an informed MMR decision (decision aid: effect estimate=1.09, 95% CI -1.36 to -0.82; information leaflet: effect estimate=-0.67, 95% CI -0.88 to -0.46). Trial arm was significantly, associated (p<0.001) with decisional conflict at post-intervention. Vaccination uptake was 100%, 91%, and 99% in the decision aid, leaflet and control arms, respectively (χ(2) (1, N=203)=8.69; p=0.017). Post-hoc tests revealed a statistically significant difference in uptake between the information leaflet, and the usual practice arms (p=0.04), and a near statistically significant difference between the, decision aid and leaflet arms (p=0.05). CONCLUSIONS: Parents' decisional conflict was reduced in both, the decision aid and leaflet arms. The decision aid also prompted parents to act upon that decision and, vaccinate their child. Achieving both outcomes is fundamental to the integration of immunisation, decision aids within routine practice. TRIAL REGISTRATION: ISRCTN72521372

Waterpipe smoking in students: Prevalence, risk factors, symptoms of addiction, and smoke intake. Evidence from one British university

Background: Anecdotal reports suggest waterpipe smoking is becoming common in students in western countries. The aim was to examine prevalence, risk factors, symptoms of addiction, and smoke intake. Methods: This was a cross-sectional survey of students with subsidiary survey of regular waterpipe user and survey of exhaled carbon monoxide (CO) before and after waterpipe smoking in customers of a waterpipe café. 937 students of Birmingham University completed the initial survey with a follow up of 21 regular waterpipe smokers. 63 customers of a waterpipe café near the University completed the study of CO intake. Results: 355 (37.9%, 95% confidence intervals (CI) 34.8 to 41.1%) students had tried waterpipes,the prevalence of trying rising with duration at University. 75 (8.0%, 95%CI 6.4 to 10.0%) were regular smokers, similar to the prevalence of cigarette smoking (9.4%). Although cigarette smoking was the major risk factor for being a regular waterpipe smoker, odds ratio (95%CI) 2.77 (1.52 to 5.06), 65% of waterpipe smokers did not smoke cigarettes. Seven of 21 (33.3%) regular waterpipe smokers experienced cravings. Nearly all regular waterpipe users thought it less harmful than smoking cigarettes. The mean (standard deviation) rise in CO was 37.4 (25.8)ppm, nearly twice as high as a typical cigarette smoker seeking cessation treatment. Conclusion: Waterpipe smoking is a common part of student culture in one British university, as in the Middle East and in the United States. It poses a potential threat to public health, with evidence of dependence and high smoke intake

What Drives the Intensification of Mesoscale Convective Systems over the West African Sahel under Climate Change?

Extreme rainfall is expected to increase under climate change, carrying potential socioeconomic risks. However, the magnitude of increase is uncertain. Over recent decades, extreme storms over the West African Sahel have increased in frequency, with increased vertical wind shear shown to be a cause. Drier midlevels, stronger cold pools, and increased storm organization have also been observed. Global models do not capture the potential effects of lower- to midtropospheric wind shear or cold pools on storm organization since they parameterize convection. Here we use the first convection-permitting simulations of African climate change to understand how changes in thermodynamics and storm dynamics affect future extreme Sahelian rainfall. The model, which simulates warming associated with representative concentration pathway 8.5 (RCP8.5) until the end of the twenty-first century, projects a 28% increase of the extreme rain rate of MCSs. The Sahel moisture change on average follows Clausius–Clapeyron scaling, but has regional heterogeneity. Rain rates scale with the product of time-of-storm total column water (TCW) and in-storm vertical velocity. Additionally, prestorm wind shear and convective available potential energy both modulate in-storm vertical velocity. Although wind shear affects cloud-top temperatures within our model, it has no direct correlation with precipitation rates. In our model, projected future increase in TCW is the primary explanation for increased rain rates. Finally, although colder cold pools are modeled in the future climate, we see no significant change in near-surface winds, highlighting avenues for future research on convection-permitting modeling of storm dynamics

Modelling of the cancer cell cycle as a tool for rational drug development: A systems pharmacology approach to cyclotherapy

The dynamic of cancer is intimately linked to a dysregulation of the cell cycle and signalling pathways. It has been argued that selectivity of treatments could exploit loss of checkpoint function in cancer cells, a concept termed "cyclotherapy". Quantitative approaches that describe these dysregulations can provide guidance in the design of novel or existing cancer therapies. We describe and illustrate this strategy via a mathematical model of the cell cycle that includes descriptions of the G1-S checkpoint and the spindle assembly checkpoint (SAC), the EGF signalling pathway and apoptosis. We incorporated sites of action of four drugs (palbociclib, gemcitabine, paclitaxel and actinomycin D) to illustrate potential applications of this approach. We show how drug effects on multiple cell populations can be simulated, facilitating simultaneous prediction of effects on normal and transformed cells. The consequences of aberrant signalling pathways or of altered expression of pro- or anti-apoptotic proteins can thus be compared. We suggest that this approach, particularly if used in conjunction with pharmacokinetic modelling, could be used to predict effects of specific oncogene expression patterns on drug response. The strategy could be used to search for synthetic lethality and optimise combination protocol designs

An audio-visual system for object-based audio : from recording to listening

Object-based audio is an emerging representation for audio content, where content is represented in a reproduction format-agnostic way and, thus, produced once for consumption on many different kinds of devices. This affords new opportunities for immersive, personalized, and interactive listening experiences. This paper introduces an end-to-end object-based spatial audio pipeline, from sound recording to listening. A high-level system architecture is proposed, which includes novel audiovisual interfaces to support object-based capture and listenertracked rendering, and incorporates a proposed component for objectification, that is, recording content directly into an object-based form. Text-based and extensible metadata enable communication between the system components. An open architecture for object rendering is also proposed. The system’s capabilities are evaluated in two parts. First, listener-tracked reproduction of metadata automatically estimated from two moving talkers is evaluated using an objective binaural localization model. Second, object-based scene capture with audio extracted using blind source separation (to remix between two talkers) and beamforming (to remix a recording of a jazz group) is evaluate

Non-specific low back pain in primary care in the Spanish National Health Service: a prospective study on clinical outcomes and determinants of management

BACKGROUND: The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months. METHODS: A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave. RESULTS: Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and, to a lesser extent, the intensity of the pain (especially leg pain), a positive straight leg raising test, and degree of disability. The main determinant of sick leave was the degree of disability, followed by the characteristics of the labor contract and the intensity of leg pain (but not low back pain). After at least 2 months of treatment, 37% of patients were still in pain and approximately 10% of patients had not improved or had worsened. CONCLUSION: Although the use of X-Rays is high, determinants of physicians' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence-based recommendations. However, after 2 months of treatment more than one third of patients continued to have back pain and about 10% had worsened

Barrett’s oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux

Abstract Background Early detection of oesophageal cancer improves outcomes; however, the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett’s oesophagus (BE) is not clear. The Cytosponge, a novel non-endoscopic sponge device, combined with the biomarker Trefoil Factor 3 (TFF3) has been tested in four clinical studies. It was found to be safe, accurate and acceptable to patients. The aim of the BEST3 trial is to evaluate if the offer of a Cytosponge-TFF3 test in primary care for patients on long term acid suppressants leads to an increase in the number of patients diagnosed with BE. Methods The BEST3 trial is a pragmatic multi-site cluster-randomised controlled trial set in primary care in England. Approximately 120 practices will be randomised 1:1 to either the intervention arm, invitation to a Cytosponge-TFF3 test, or the control arm usual care. Inclusion criteria are men and women aged 50 or over with records of at least 6 months of prescriptions for acid-suppressants in the last year. Patients in the intervention arm will receive an invitation to have a Cytosponge-TFF3 test in their general practice. Patients with a positive TFF3 test will receive an invitation for an upper gastro-intestinal endoscopy at their local hospital-based endoscopy clinic to test for BE. The primary objective is to compare histologically confirmed BE diagnosis between the intervention and control arms to determine whether the offer of the Cytosponge-TFF3 test in primary care results in an increase in BE diagnosis within 12 months of study entry. Discussion The BEST3 trial is a well-powered pragmatic trial testing the use of the Cytosponge-TFF3 test in the same population that we envisage it being used in clinical practice. The data generated from this trial will enable NICE and other clinical bodies to decide whether this test is suitable for routine clinical use. Trial registration This trial was prospectively registered with the ISRCTN Registry on 19/01/2017, trial number ISRCTN68382401

Validation of Results from Knowledge Discovery: Mass Density as a Predictor of Breast Cancer

The purpose of our study is to identify and quantify the association between high breast mass density and breast malignancy using inductive logic programming (ILP) and conditional probabilities, and validate this association in an independent dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set the Aleph ILP system to generate 10,000 rules per malignant finding with a recall >5% and precision >25%. Aleph reported the best rule for each malignant finding. A total of 80 unique rules were learned. A radiologist reviewed all rules and identified potentially interesting rules. High breast mass density appeared in 24% of the learned rules. We confirmed each interesting rule by calculating the probability of malignancy given each mammographic descriptor. High mass density was the fifth highest ranked predictor. To validate the association between mass density and malignancy in an independent dataset, we collected data from 180 consecutive breast biopsies performed between 2005 and 2007. We created a logistic model with benign or malignant outcome as the dependent variable while controlling for potentially confounding factors. We calculated odds ratios based on dichomotized variables. In our logistic regression model, the independent predictors high breast mass density (OR 6.6, CI 2.5–17.6), irregular mass shape (OR 10.0, CI 3.4–29.5), spiculated mass margin (OR 20.4, CI 1.9–222.8), and subject age (β = 0.09, p < 0.0001) significantly predicted malignancy. Both ILP and conditional probabilities show that high breast mass density is an important adjunct predictor of malignancy, and this association is confirmed in an independent data set of prospectively collected mammographic findings

Cluster randomized evaluation of Adolescent Girls Empowerment Programme (AGEP): study protocol.

BACKGROUND: Adolescents in less developed countries such as Zambia often face multi-faceted challenges for achieving successful transitions through adolescence to early adulthood. The literature has noted the need to introduce interventions during this period, particularly for adolescent girls, with the perspective that such investments have significant economic, social and health returns to society. The Adolescent Girls Empowerment Programme (AGEP) was an intervention designed as a catalyst for change for adolescent girls through themselves, to their family and community. METHODS/DESIGN: AGEP was a multi-sectoral intervention targeting over 10,000 vulnerable adolescent girls ages 10-19 in rural and urban areas, in four of the ten provinces of Zambia. At the core of AGEP were mentor-led, weekly girls' group meetings of 20 to 30 adolescent girls participating over two years. Three curricula - sexual and reproductive health and lifeskills, financial literacy, and nutrition - guided the meetings. An engaging and participatory pedagogical approach was used. Two additional program components, a health voucher and a bank account, were offered to some girls to provide direct mechanisms to improve access to health and financial services. Embedded within AGEP was a rigorous multi-arm randomised cluster trial with randomization to different combinations of programme arms. The study was powered to assess the impact across a set of key longer-term outcomes, including early marriage and first birth, contraceptive use, educational attainment and acquisition of HIV and HSV-2. Baseline behavioural surveys and biological specimen collection were initiated in 2013. Impact was evaluated immediately after the program ended in 2015 and will be evaluated again after two additional years of follow-up in 2017. The primary analysis is intent-to-treat. Qualitative data are being collected in 2013, 2015 and 2017 to inform the programme implementation and the quantitative findings. An economic evaluation will evaluate the incremental cost-effectiveness of each component of the intervention. DISCUSSION: The AGEP program and embedded evaluation will provide detailed information regarding interventions for adolescent girls in developing country settings. It will provide a rich information and data source on adolescent girls and its related findings will inform policy-makers, health professionals, donors and other stakeholders. TRIAL REGISTRATION: ISRCTN29322231 . March 04 2016; retrospectively registered